Understanding the Association of Plasmid Incompatibility Groups With Variable Antimicrobial Resistance Genotypes in Bacteria

Plasmids play an essential role in the spread of antimicrobial resistance (AMR) by facilitating the horizontal transfer of resistance genes between bacterial environments. However, large-scale investigations into the association between plasmid incompatibility groups (Inc groups) and specific resistance profiles remain limited. In this study, we analyzed 28,047 plasmid sequences from publicly available whole-genome sequencing data sets, identifying incompatibility groups in 11,288 plasmids using in silico replicon typing. Our results revealed that the majority of plasmids harbored a single replicon, while a substantial fraction carried multiple replicons, predominantly two. We evaluated the relationship between plasmid replicon spillovers and their role in the spread of resistance genes. Our results revealed that plasmids with five replicons have a significantly higher resistance potential (60%) compared to plasmids with fewer replicons, decreasing their adaptability and propensity for cointegration, which facilitates horizontal gene transfer. Among the resistance-associated plasmids, the IncF, IncI, and IncH families were predominant and acted as effective carriers of resistance genes. Comparative analyses between resistant and non-resistant plasmids did not reveal a clear visual pattern of association between the most prevalent Inc groups and specific antimicrobial classes, indicating that such relationships are shaped by contextual factors, including selective instructions, bacterial host diversity, and distribution. These findings highlight the complexity of the spread of plasmid-mediated AMR and highlight the need for integrated genomic and epidemiological approaches to better understand the ecological and evolutionary dynamics that influence the spread of resistance genes.